Transcript Endophthalmitis prophylaxis

DR Hamid Aryaei Tabar MD…assistant professor of ophthalmology
KUMS
‫کرمانشاه طاق بستان‬
Prophylaxis for post operative
endophthalmitis
Endophthalmitis prophylaxis

What is evidence

Case selection (preoperation)…..treat any condition which may result in
endophthalmitis

Operatin room

Preop antibiotics
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Personell
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Equipments (disposable or not )
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Prep&drape
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Teqnique of surgery
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Post op (patient instructions . Antibiotics choices & how long should be )
Evidences
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Endophthalmitis following cataract surgery fortunately has
declined over the past 30 years.

The incidence rate has declined from approximately 0.3%
during the Intracapsular-extraction era (1950-1980) to
0.1% during the extracapsular era (1980-1995) to 0.05%
rate during the current period of small incision
phacoemulsification/foldable intraocular lenses (19952012).
As the size of the cataract incision grows smaller, the
average interval between surgery and the clinical onset of
endophthalmitis has risen from 3-7 days (before 1995) to
7-14 days (after 1995).
 [2]

This observation suggests that in the large-incision
intracapsular and extracapsular eras, the causative
bacteria gained access to the interior of the eye at the
time of surgery
EVIDENCE

In the most recent small-incision era, the causative bacteria are more
likely to gain delayed access to the interior of the eye through an
incompetent or leaking, unsutured clear corneal small incision

.The shift in timing indicates that "early-onset" postoperative
endophthalmitis is more likely to be acquired during surgery, and
later-onset infection is hypothesized to originate from inward
absorption of contaminated tears from the surface of the eye through
a leaky incision.

The bacteria responsible for endophthalmitis, Staphylococcus
epidermidis and Staphylococcus aureus, are representative of the
usual bacterial flora inhabiting the normal conjunctiva.

As the overall incidence of postoperative endophthalmitis has waned
during the past 30 years, the incidence of drug resistance of these
offending organisms has dramatically increased

. Methicillin-resistant S aureus (MRSA) and methicillin-resistant S
epidermidis (MRSE) now constitute more than 50% of offending
isolates from postoperative endophthalmitis. Virtually all methicillinresistant organisms are also resistant to cephalosporins, such as
cefazolin and cefuroxime.
Evidences(tan and co-workers……)

Tan and coworkers reviewed 50,177 sequential cataract surgeries performed at the Tan Tock Seng
Hospital in Singapore during an 11-year period.

They compared endophthalmitis rates before the routine use of intracameral cefazolin injection
at the conclusion of cataract surgery with rates during the subsequent period when intracameral
cefazolin was routinely administered.

Injected eyes received 1.0 mg of cefazolin in a volume of 0.1 mL, injected into the capsular bag
at the conclusion of the cataract surgery

Both the injection and the noninjection groups received subconjunctival gentamicin, 8.0 mg, at
the end of the procedure.
7
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The noninjection group (29,539) underwent surgery between 1999 and 2006 and the injection
group (20,638) between 2006 and 2010.

Most cases (85%) were performed with a clear corneal incision, and the remainder were
extracapsular extractions.

The incidence of endophthalmitis was 0.064% (19 cases, predominantly gram-positive organisms)
in the noninjected group and 0.01% (2 cases, Pseudomonas aeruginosa and Streptococcus mitis) in
the cefazolin-injected group (P = .003).
Evidences(Swedish study)

cefuroxime was injected intracamerally at the conclusion of cataract surgery,
resulting in a significant reduction in postoperative endophthalmitis compared
with patients who did not receive the drug.

In all of these studies, including this study by Tan and colleagues, the antibiotic
would be expected to be active against susceptible gram-positive organisms that
are present in the anterior chamber at the end of surgery.

Because the antibiotic remains in adequate concentrations for less than an hour
as a result of progressive dilution, any organisms introduced thereafter would not
be expected to be suppressed by the antibiotic.

Inhibition of later-onset endophthalmitis would depend on preventing access of
pathogenic organisms present in the tear film to the interior of the eye through
the incision.

This could be accomplished by ensuring tight closure of the incision and/or
suppression of bacterial growth in the tear film through the use of prophylactic
topical antibiotics.
Evidences( US and etc)

The success of intraocular cephalosporin injection in significantly reducing rates of
postoperative endophthalmitis in studies performed outside the United States is
very compelling and supports its continued use in these countries.

In all of these studies, however, the rates of endophthalmitis in the untreated
group are higher than in treated groups in the United States.

Comparable trials have not been performed to date in the United States, so the
efficacy of similar prophylactic treatment is not established here.

Furthermore, only methicillin-sensitive, gram-positive organisms would be
suppressed, and later-onset, through-the-incision infections would not be
prevented.

Given the apparent safety of the intraocular injection regimen with these
antibiotics, without reported cases of overdosage or toxic anterior segment
syndrome, North American ophthalmologists should probably reconsider their
traditional resistance to this prophylactic therapy.
Evidences ESCRS multicenter study and identification of risk
factors

To identify risk factors and describe the effects of antibiotic prophylaxis on the
incidence of postoperative endophthalmitis after cataract surgery based on analysis
of the findings of the European Society of Cataract & Refractive Surgeons (ESCRS)
multicenter study.

SETTING: Twenty-four ophthalmology units in Austria, Belgium, Germany, Italy,
Poland, Portugal, Spain, Turkey, and the United Kingdom.
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METHODS: A prospective randomized partially masked multicenter cataract surgery
study recruited 16 603 patients.
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The study was based on a 2 x 2 factorial design, with intracameral cefuroxime and
topical perioperative levofloxacin factors resulting in 4 treatment groups.
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The comparison of case and non-case data was performed using multivariable
logistic regression analyses. Odds ratios (ORs) associated with treatment effects
and other risk factors were estimated.
Evidences( ESCRS ….)
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RESULTS: Twenty-nine patients presented with endophthalmitis, of whom 20 were classified as
having proven infective endophthalmitis.

The absence of an intracameral cefuroxime prophylactic regimen at 1 mg in 0.1 mL normal saline
was associated with a 4.92-fold increase (95% confidence interval [CI], 1.87-12.9) in the risk for total
postoperative endophthalmitis.

In addition, the use of clear corneal incisions (CCIs) compared to scleral tunnels was associated with
a 5.88-fold increase (95% CI, 1.34-25.9) in risk and the use of silicone intraocular lens (IOL) optic
material compared to acrylic with a 3.13-fold increase (95% CI, 1.47-6.67). The presence of surgical
complications increased the risk for total endophthalmitis 4.95-fold (95% CI, 1.68-14.6), and more
experienced surgeons were more likely to be associated with endophthalmitis cases.

When considering only provematerial were significantly associated with an increased risk, and there
was evidence that men were more predisposed to infection (OR, 2.70; 95% CI, 1.07-6.8).

CONCLUSIONS: Use of intracameral cefuroxime at the end of surgery reduced the occurrence of
postoperative endophthalmitis. Additional risk factors associated with endophthalmitis after
cataract surgery included CCIs and the use of silicone IOLs.

n infective endophthalmitis cases, the absence of cefuroxime and the use of silicone IOL optic
EVIDENCES[Levofloxacin (oftaquix) a
fluoroquinolone of a new generation in
prevention of the postoperative
endophthalmitis following uncomplicated
cataract surgery--the study of the European
Society of Cataract and Refractive Surgeons
(ESCRS)].
Evidences

Abstract Randomised multi-centre european clinical trial of antibiotic prophylaxis
for endophthalmitis following cataract surgery - study has just begun in Poland.

Poland is joining one of the largest prospective european clinical study of antibiotic
prophylaxis and the largest in ophthalmology - the ESCRS endophthalmitis
prophylaxis clinical trial.
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Up to 35 000 cataract patients are going to be recruited for this randomized,
controlled, multi-centre study in 16 centres from 10 european countries. The goal is
to reduce the incidence of endophthalmitis after cataract phacoemusification in
Europe to less than 0.05% (less than 1 per 2 000 surgeries).

The patients will be divided into four groups; different regimes of two antibiotics:
cefuroxime injected intra-camerally and levofloxacine eye
drops topically will be compared.
What we can do for prevention
Treat any eye conditions which may
associated with post op endophthalmitis
What are the main risk factors for
occurrence of post operative
endophthalmitis
Risk Factors for Acute Endophthalmitis following Cataract
Surgery: A Systematic Review and Meta-Analysis

He cao & etc Aug 2013

A total of 6 686 169 participants with 8 963 endophthalmitis in 42 studies were analyzed. Of the nine risk factors
identified in our systematic review and meta-analysis
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Extra- or intracapsular cataract extraction
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clear corneal incision,
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without intracameral cefazolin (1 mg in 0.1 ml solution),

without intracameral cefuroxime (1 mg in 0.1 ml solution),
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post capsular rupture,

silicone intraocular lenses


intraoperative complications were found strongly associated with acute endophthalmitis.
Other significant factors with a lower strength of association (risk estimates generally 1.5 or less) were male
gender and old age (85 years and older).
Risk factors for development of posttrabeculectomy endophthalmitis
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


These results provide strong evidence of an increased risk of late
endophthalmitis in patients who have
diabetes mellitus
or have had an episode of blebitis
and suggest antiproliferative agents may also have an important role
Role of prophylavtic antibiotics

Some surgeons use topical drops 2 hours before surgery (every 15
minutes ) and after surgery every hour for 24 ….then every 4 hour for
one week

Prolong administration of antibiotics before surgery may lead to
resistance
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Some give 3 days before surgery
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Some 1drop every 5 minutes 1 hours before surgery

Recent studies shows emergence of resistence to flouroquinolones in 30
percent of staph
Prevention of endophthalmitis by collagen shields presoaked in fourthgeneration fluoroquinolones versus by topical prophylaxis

Forty rabbits received bilateral 0.03 mL intracameral injections of Staphylococcus
epidermidis (5 × 108 colony-forming units). Four groups of 10 rabbits had their eyes
randomized to receive (1) 3 mg/mL gatifloxacin (Zymar) drops or shield in Zymar, (2)
Zymar drops or shield in 10 mg/mL gatifloxacin (Tequin), (3) 5 mg/mL moxifloxacin
(Vigamox) drops or shield in Vigamox, or (4) balanced salt solution (BSS) drops or shield
in BSS. Each eye received Zymar, Vigamox, or BSS 4 times 1 hour before injection. The
antibiotic–BSS was administered every 2 hours (5 doses total). One day later, signs of
endophthalmitis were scored under the slitlamp.

Results
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Groups 1 and 2 had significantly lower endophthalmitis incidences (total score ≥8) than
the BSS controls. Shield scores were not significantly different from those of the
counterpart drops. The comparison between drops was not significant (P = .0513); the
difference between shields (P = .0232) and the post-comparison Zymar versus BSS shields
(P = .0021) were significant.
Primary Prevention

Prevention of postoperative infectious endophthalmitis is a subject that all
intraocular surgeons need to address in their surgical practice

. Surgeons institute a wide variety of techniques intended to prevent
endophthalmitis, and there is not one single regimen that is universally
agreed upon for this purpose.

Many studies have been performed to address the efficacy of various
prophylactic protocols; however there are numerous inherent complexities in
designing high quality clinical trials to address this issue

. Endophthalmitis is a rare entity, thus generating high powered studies is
challenging. Also, differences in surgical technique vary widely between
surgeons, and controlling for these factors can be difficult

Many studies have used surrogate measures for endophthalmitis, such as
cultures of periocular flora or anterior chamber sampling. Other studies use
animal models, so the results may not be perfectly applicable to the human
eye. There are no placebo controlled, double blinded, randomized clinical
trials that compare all the currently used methods of endophthalmitis
prophylaxis.

difficult to make solid recommendations about the gold standard of care.
Preoperative Regimens
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reduction of resident flora on the lids, lashes, and the ocular surface.

meticulous lid hygiene prior to surgery. This treatment is aimed at reducing
blepharitis, with the added benefit of enhancing the health of the surface tear
film through concomitant treatment of meibomian gland dysfunction

Warm soaks with simple lid scrubs directed at the base of the lashes, utilizing a
washcloth with a gentle soap can be instituted. Commercial over-the-counter
eyelid cleaners are available for this purpose.

Preoperative topical antibiotic regimens are often instituted. There are no wellcontrolled high quality studies that have definitely shown a benefit in
preoperative (or postoperative) topical antibiotics in the prevention of cultureproven endophthalmitis

reduced cultures of periocular flora with administration of preoperative topical
antibiotics [1].

Duration of preoperative administration vary: some surgeons begin dosaging 1
hour prior to surgery, other recommend starting 1-3 days prior to surgery. Some
surgeons feel that the extra cost to the patient and society associated with
preoperative topical antibiotics and the lack of any data suggesting efficacy are
reason to not recommend this regimen

. Others worry that preoperative exposure to an antimicrobial agent that will
again be used postoperatively may help select for resistant organisms
postoperatively, thereby negating any benefit of a preoperative course

Without quality data, a standard-of-care has not been established.
wound
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Placed at the limbus
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Have multiple planes (3 ideal)
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Have as long a tunnel as possible
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Length equaling the width of the incision
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Self-sealing at normal IOP
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Minimal hydration required
Perioperative Regimens

Once the patient is in the operating room, proper sterile preparation of the surgical
site is of utmost importance.

Instillation of Povidone-Iodine 5% onto the ocular surface at least 3-5 minutes prior
to surgery is recommended.

This measure has the most long-standing and highest quality evidence to support its
efficacy [2].

In addition, sterile preparation of the skin surrounding the surgical eye with
Povidone-Iodine 10% is often utilized.


Meticulous draping of the lids and eyelashes is performed to achieve a sterile field.
Eyelash trimming has not been determined to reduce the bacterial flora and is not
recommended
Surgical Regimens

Meticulous attention should be paid to the construction of the incisions. In modern day
phacoemulsification, small incision surgeries have evolved, which often do not require sutures to
achieve a water-tight seal at the end of the surgery.

However, with the increase in use of clear corneal incisions, there has thought to have been a
concomitant rise in the rate of endophthalmitis just after the turn of the century, especially as
compared to scleral tunnel incisions (Cooper et al).

Defects in the clear corneal wound are postulated to be a risk factor for the development of
endophthalmitis, allowing pathogens to enter the anterior chamber after surgery.

Wound gape, leak, dehiscence, and vitreous wicks have been found in association with
endophthalmitis (Maxwell et al).

At the end of surgery, after the eye is re-inflated to physiologic pressure, surgeons will often
perform hydration of the wound, Seidel testing for leakage, or check the wounds with a dry
sponge to assess for wound leak.

There is evidence that the effect of stromal hydration lasted for at least 1 week after surgery[4].

There is also evidence to suggest that slightly elevated intraocular pressure at the end of surgery
can help to seal the wound through improvement in the internal architecture (McDonnell et al).
When there is evidence of wound leak or concerns about the integrity of the wound, it is prudent
to place a single interrupted suture at the end of the surgery. This suture can be removed 1 week
after surgery after the wound has a chance to seal, however this wound should be Seidel tested
after the suture has been removed, to ensure that the wound has adequately healed
Surgical regimens

Some surgeons have advocated the use of antibiotics in the irrigation fluid during surgery, however there are no
robust studies showing efficacy.

Vancomycin is considered to be a last line of defense for resistant organisms, and widespread use of this
powerful antibiotic in routine cataract surgery comes with the risk of development of vancomycin resistant
organisms.

The use of vancomycin as a prophylactic measure in the irrigation fluid is not recommended on a routine
basis[5].
Surgical regimens

The only large, prospective, randomized, study examining the efficacy of
endophthalmitis prophylaxis was released by the European Society of Cataract
and Refractive Surgeons in 2006.

The landmark study was based on work by Per Montan, MD in Sweden. The
injection of intracameral cefuroxime into the anterior chamber at the end of
surgery reduced the occurrence of endophthalmitis (Peter Barry, MD and the
ESCRS Endophthalmitis Study Group).

Following publication of the ESCRS study, intracameral injection had not
been widely adopted in the United States for various reasons, including
concerns over the need to compound this medication, the risk of TASS, and
the spectrum of activity of this class of antibiotics[6]

. A US study published in 2013, however showed similar results to the
European study[7].
Surgical regimens

Intracameral moxifloxacin has also been used for prophylaxis with a good
safety profile[8], (Lane et al).

The potential advantages of moxifloxacin are better Gram negative coverage,
in particular enterococcus, and ease of preparation as the drug can be drawn
up undiluted from a commercially available preparation[9].

Subconjunctival antibiotic injections have been popular in the past, but there
is a paucity of high powered, large controlled studies to make a definitive
statement about the role of these injections in the prevention of
endophthalmitis
Postoperative Regimens

Postoperative topical antibiotic regimens are intended to reduce the bacterial
burden during the time it takes for the surgical incision to re-epithelialize.

There are no high quality studies that indisputably demonstrate the
effectiveness of this strategy in preventing endophthalmitis.

It is often recommended that patients continue their antibiotic drops for 1
week after surgery.
At the end of surgery

Again look for hypotonia

Especially when you remove the lid speculum

Look for any remaining debrices which was comes from meibomien glands by the
pressure of lid speculum

Instill 5% betadineASAP & first

Inject air?

Remove drape and look again

Start topical drops ASAP
Potential Complications of Intracameral
Antibiotics
1. Fungal Contamination during mixing
2. Incorrect preparation and dosage
3. Allergy
4. Cystoid macular edema
5. Corneal edema
prophylaxis

povidone-iodine received the highest
evidence rating.
All other reported prophylactic interventions,
including preoperative topical antibiotics received
the lowest clinical recommendation based on
weak and often conflicting evidence justifying
their use.”
Preoperative
flouroqinolones
•
Bactericidal
•
Inhibit DNA synthesis (DNA gyrase)
•
Broad spectrum of activity in vitro
•
Low toxicity
•
Excellent penetration
First generation

cinoxacin and nalidixic acid

oldest and least often used quinolones

minimal serum levels are achieved

use of these drugs has been restricted to the treatment of uncomplicated
urinary tract infections.

Cinoxacin and nalidixic acid require more frequent dosing than the newer
quinolones, and they are more susceptible to the development of bacterial
resistance.

These agents are not recommended for use in patients with poor renal
function because of significantly decreased urine concentrations.
Second generation

increased gram-negative activity, as well as some gram-positive and atypical pathogen coverage.

Compared with first-generation drugs and considered as a group, these agents have broader clinical
applications in the treatment of complicated urinary tract infections and pyelonephritis, sexually
transmitted diseases, selected pneumonias and skin infections.

Second-generation agents include ciprofloxacin, enoxacin, lomefloxacin, norfloxacin and ofloxacin

Ciprofloxacin is the most potent fluoroquinolone against P. aeruginosa Because of its good
penetration into bone, orally administered ciprofloxacin is a useful alternative to parenterally
administered antibiotics for the treatment of osteomyelitis caused by susceptible organisms.

Although the FDA has labeled some second-generation quinolones for the treatment of lower
respiratory tract infections and acute sinusitis, it should be stressed that S. pneumoniae is
frequently resistant to agents in this class. Consequently, second-generation quinolones are not the
drugs of first choice for lower respiratory tract infections and acute sinusitis.

Of the second-generation agents, ofloxacin has the greatest activity against Chlamydia trachomatis.

Ciprofloxacin and ofloxacin are the most widely used second-generation quinolones because of their
availability in oral and intravenous formulations and their broad set of FDA-labeled indications.
Third generation

levofloxacin, gatifloxacin, moxifloxacin and sparfloxacin.

These agents are separated into a third class because of their expanded activity against gram-positive
organisms, particularly penicillin-sensitive and penicillin-resistant S. pneumoniae, and atypical pathogens
such as Mycoplasma pneumoniae and Chlamydia pneumoniae

Although the third-generation quinolones retain broad gram-negative coverage, they are less active than
ciprofloxacin against Pseudomonas species.

Because of their expanded antimicrobial spectrum, third-generation quinolones are useful in the
treatment of community-acquired pneumonia, acute sinusitis and acute exacerbations of chronic
bronchitis, which are their primary FDA-labeled indications.

Gatifloxacin also has FDA-labeled indications for urinary tract infections and gonorrhea.

Levofloxacin (the more active component of the ofloxacin racemic mixture) and gatifloxacin are available
in oral and intravenous formulations.

Sparfloxacin carries a significant risk of phototoxicity.

Grepafloxacin, sparfloxacin and moxifloxacin have been reported to cause prolongation of the QT
interval; gatifloxacin has not.

However, the FDA recommends that all of these drugs should be avoided in patients who are taking drugs
that are known to prolong the QT interval, such as tricyclic antidepressants, phenothiazines and class I
antiarrhythmics.

In contrast, levofloxacin does not affect the QT interval
Fourth generation

Trovafloxacin, currently the only member of the fourth-generation class

adds significant antimicrobial activity against anaerobes while maintaining the gram-positive and gramnegative activity of the third-generation quinolones.

It also retains activity against Pseudomonas species comparable to that of ciprofloxacin.17,18

Trovafloxacin is available in an oral tablet and as the prodrug alatrofloxacin (Trovan IV) in an intravenous
formulation.

Although the findings of few clinical trials on trovafloxacin have been published, the drug was originally
labeled by the FDA for the treatment of a wide spectrum of infectious diseases.

Because of concern about hepatotoxicity, trovafloxacin therapy should be reserved for life- or limbthreatening infections requiring inpatient treatment (hospital or long-term care facility)

drug should be taken for no longer than 14 days.
Next generation

Levofloxacin, sparfloxacin, gatifloxacin, moxifloxicin, others

Enhanced pharmacokinetics

Improved Gram-positive antimicrobial activity

Responsible and appropriate prescribing and dosing essential (regardless of
agent)
How to avoid resistant strain emergence)
•
Minimum dosage four times a day
•
Maximum time course – 2 weeks
•
Never taper dose
Intra cameral
moxifloxacin
moxifloxacin
Which one you prefer



Preoperative

Oral

Topical
Intraoperative

Intracameral via the irrigating solution

Subconjunctival
Perioperative


Topical
Postoperative

Topical
Thank you for your attention
BY : DR Hamid Aryaei Tabar MD ,
KUMS